Breast cancer is one of the most common malignant tumors in women. More than one million new cases of breast cancer occur worldwide annually, and nearly 400 thousand people die from breast cancer every year. In recent years, the worldwide incidence of breast cancer showed a clear upward trend. Notwithstanding whether the incidence of breast cancer generally higher or lower than average in a particular region, the incidence of breast cancer is increasing at a rate of 5-20%. The growth trend of the incidence of breast cancer in Asian women has been significantly higher than that in the United States and Europe. In some cities in China, breast cancer has become the primary malignant tumor in women. Conventional treatments for breast cancer include surgery, chemotherapy and endocrine therapy and so on. Although these conventional treatments may prolong survival in patients to a large extent, their side effects are often serious. Also, the therapeutic effect of many may be hard to further improve. Targeted cancer therapy is a new treatment for cancer that has arisen in recent years. A representative of targeted cancer therapy is antitumor monoclonal antibody therapy.
HER2 (human epidermal growth factor receptor 2) is a transmembrane protein with tyrosine kinase activity, having a molecular weight of about 185 KD. Anti-HER2 humanized monoclonal antibody specifically bind to HER2, and may have antitumor mechanisms as follows: specifically binding to the extracellular domain of HER2 receptor to block the constitutive activation of HER2 homodimers and interfere the heterodimer formation of HER2 with other ErbB family members; mediating the endocytosis and the degradation in lysosomes of HER2 receptor; activating PTEN (phosphatase and tensin homology) and blocking PI3K (Phosphatidylinositol 3-kinase) signal channel; inhibiting tumor cell proliferation by regulation of cell cycle; promoting tumor cell apoptosis; inhibiting tumor angiogenesis; ADCC (antibody-dependent cell-mediated cytotoxicity) effect; inhibiting DNA repair; increasing the cytotoxicity of chemotherapeutic agents; reversing the resistance of tumor cells to the killing effects of host cell factors, and etc.
Trastuzumab (trade name: Herceptin) is a humanized anti-HER2 antibody that maintains the murine CDR regions and a small amount of murine FR residues, which has been used to treat patients with HER2 overexpressing metastatic breast cancer as single drug. This drug may be used in combination with paclitaxel or anthracyclines (doxorubicin or epirubicin) plus cyclophosphamide in clinic as first-line drugs to treat HER2 overexpressing metastatic breast cancer. Because of primary or acquired resistance to Trastuzumab, combination therapy of Trastuzumab and Pertuzumab use for treatment of breast cancer.